First-pass effects of verapamil on the intestinal absorption and liver disposition of fexofenadine in the porcine model

Drug Metabolism and Disposition : the Biological Fate of Chemicals
Niclas PetriHans Lennernäs

Abstract

The aim of this study in pigs was to investigate the local pharmacokinetics of fexofenadine in the intestine and liver by using the pig as a model for drug transport in the entero-hepatobiliary system. A parallel group design included seven pigs (10-12 weeks, 22.2-29.5 kg) in three groups (G1, G2, G3), and a jejunal single-pass perfusion combined with sampling from the bile duct and the portal, hepatic, and superior caval veins was performed. Fexofenadine was perfused through the jejunal segment alone (G1: 120 mg/l, total dose 24 mg) or with two different verapamil doses (G2: 175 mg/l, total dose 35 mg; and G3: 1000 mg/l, total dose 200 mg). The animals were fully anesthetized and monitored throughout the experiment. Fexofenadine had a low liver extraction (E(H); mean +/- S.E.M.), and the given doses of verapamil did not affect the E(H) (0.13 +/- 0.04, 0.16 +/- 0.03, and 0.12 +/- 0.02 for G1, G2, and G3, respectively) or biliary clearance. The E(H) for verapamil and antipyrine agreed well with human in vivo data. Verapamil did not increase the intestinal absorption of fexofenadine, even though the jejunal permeability of fexofenadine, verapamil, and antipyrine showed a tendency to increase in G2. This combined perfusion and hep...Continue Reading

References

Oct 1, 1992·Pharmaceutical Research·H LennernäsL K Paalzow
Jun 7, 1996·Biochimica Et Biophysica Acta·S Childs, V Ling
Oct 1, 1996·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·M F FrommM Eichelbaum
Sep 1, 1996·Pharmaceutical Research·U FagerholmH Lennernäs
Jul 1, 1997·The Journal of Pharmacy and Pharmacology·H Lennernäs
Aug 28, 1998·The Journal of Pharmacy and Pharmacology·R SandströmH Lennernäs
Aug 28, 1998·The Journal of Pharmacy and Pharmacology·A LindahlH Lennernäs
Jul 27, 1999·British Journal of Clinical Pharmacology·R SandströmH Lennernäs
Aug 10, 2000·The British Journal of Surgery·L R JiaoN Habib
Mar 10, 2001·Clinical Pharmacology and Therapeutics·M A HammanS D Hall
Jun 28, 2002·Clinical Pharmacology and Therapeutics·Zaiqi WangStephen D Hall
Nov 5, 2002·Journal of Clinical Pharmacology·Michael D PerloffDavid J Greenblatt
Jan 1, 2003·Biochimica Et Biophysica Acta·B Hagenbuch, P J Meier
Feb 13, 2003·British Journal of Clinical Pharmacology·Christer TannergrenHans Lennernäs
May 2, 2003·The Journal of Pharmacology and Experimental Therapeutics·Daisuke KobayashiIkumi Tamai
Aug 2, 2003·The New England Journal of Medicine·William M Lee
Oct 31, 2003·Clinical Pharmacology and Therapeutics·Christer TannergrenHans Lennernäs
Nov 12, 2003·The Journal of Pharmacology and Experimental Therapeutics·Takashi NozawaIkumi Tamai
Nov 19, 2003·Pharmaceutical Research·Stéphane Mouly, Mary F Paine
Mar 3, 2004·Journal of Biochemical and Molecular Toxicology·Huadong TangMichael Mayersohn
Sep 14, 2004·Pharmaceutical Research·Niclas PetriHans Lennernäs
Nov 4, 2004·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Christian ZimmermannJuergen Drewe
Apr 12, 2005·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Harunobu TaharaYuichi Sugiyama
Apr 22, 2005·British Journal of Clinical Pharmacology·Mikko NiemiMartin F Fromm
Jul 15, 2005·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Maki ShimizuYuichi Sugiyama
Sep 15, 2005·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·Dirk K F Meijer, Hans Lennernäs

❮ Previous
Next ❯

Citations

Feb 25, 2014·Molecular Pharmaceutics·Ilse R DubbelboerHans Lennernäs
Jun 30, 2010·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·E BergmanH Lennernäs
Aug 18, 2012·Journal of Pharmaceutical Sciences·Rajesh KulkarniGregory T Knipp
Mar 31, 2011·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·Helena Anna ThörnHans Lennernäs
Apr 5, 2008·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·E M PerssonB Abrahamsson
Aug 29, 2006·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·Christer TannergrenHans Lennernäs
Oct 31, 2007·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·H Lennernäs
Dec 11, 2013·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·Anna LundahlMikael Hedeland
May 9, 2012·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·Helena Anna ThörnHans Lennernäs
Oct 1, 2013·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·Erik SjögrenHans Lennernäs
Mar 19, 2014·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·Erik SjögrenPeter Langguth
Dec 17, 2008·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·Anna LundahlHans Lennernäs
Feb 24, 2009·Drug and Alcohol Dependence·Evan D KharaschPamela Sheffels Bedynek
Sep 27, 2012·Molecular Pharmaceutics·Helena Anna ThörnHans Lennernäs
Sep 28, 2010·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·Caroline MacLeanGert Fricker
Apr 18, 2008·The Journal of Pharmacy and Pharmacology·Urban Fagerholm
Sep 2, 2018·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Huadong Tang, Michael Mayersohn
May 7, 2008·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Elin SjödinHans Lennernäs
Oct 28, 2010·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Elin M MatssonHans Lennernäs
Sep 24, 2009·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Ebba BergmanHans Lennernäs

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.